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PubMed1997

Preoperative pulmonary function tests do not predict outcome after coronary artery bypass.

PURPOSE: To evaluate the utility of preoperative pulmonary function tests in predicting postoperative complications and lengths of stay after coronary artery bypass grafting. METHODS: Medical records of 193 consecutive patients who underwent coronary artery bypass grafting from October 1993 to September 1994 were reviewed. Preoperative pulmonary function tests, comorbid conditions, smoking history, postoperative complications, and total days in the intensive care unit, hospital, and on mechanical ventilation were abstracted. Data were analyzed using linear regressions, analyses of variance, and nonpaired Student's t tests. RESULTS: Pulmonary function tests were normal in 56 subjects (29%, group 1), mildly impaired in 72 (37%, group 2), and moderately impaired in 35 (18%, group 3). Thirty patients (16%) had no pulmonary function tests. Group 3 subjects were older (71) compared to groups 1 and 2 (63 and 65, P < 0.05). There was no major difference in comorbid conditions or smoking status among the groups. All patients had atelectasis postoperatively. The most frequent postoperative complications were pleural effusions (43%), pulmonary edema or congestive heart failure (28%), and atrial fibrillation (35%). The repeat surgery rate was 3.6%. The mean length of hospital stay was 10.1 +/- 0.6 days, with 1.5 +/- 0.1 days of mechanical ventilation and 2.8 +/- 0.2 days of intensive care unit stay. Overall, pulmonary function tests had no predictive value for postoperative pulmonary and nonpulmonary complications, nor for durations of mechanical ventilation and intensive care unit stay. There was a trend toward increased length of hospital stay in patients with impaired pulmonary function tests (group 18.6 +/- 0.6, group 2 9.6 +/- 0.8, group 312.7 +/- 2.3 days, P = 0.09) but this was consistent with random variation. CONCLUSIONS: Preoperative pulmonary function tests were not useful in predicting postoperative outcomes in patients undergoing coronary artery bypass grafting.

Aged↗
PubMedDate not supplied

Self-deception predicts self-report and endurance of pain.

This study sought to test predictions made from disregulation and systems theories regarding self-deception and pain responsivity. Sixty-four subjects completed the L-scale of the Eysenck Personality Inventory and, based on their scores, were categorized as either High, Medium, or Low Deceptors. Both sensory threshold and three levels of affective pain judgments were determined using electrocutaneous nociceptive stimulation applied to the forearm. Results indicated that there were no differences among groups in their sensation thresholds. However, large differences in affective pain judgments emerged between High and Low Deceptors. High Deceptors differed significantly from Low Deceptors at the Tolerance (9.4 vs. 5.2 mA, p less than 0.001), Pain threshold (7.9 vs. 3.8 mA, p less than 0.001), and Discomfort (4.4 vs. 2.2 mA, p less than 0.01) judgment levels. These findings are consistent with a systems model of pain perception and are discussed in terms of the role of pain in mediating the relationship between cognitive coping patterns and recovery from illness and surgery. A possible opiate-peptide hypothesis of repressive coping & disregulation of pain is proposed.

Adaptation, Psychological↗
PubMed2002

Predicting cognitive impairment in high-functioning community-dwelling older persons: MacArthur Studies of Successful Aging.

OBJECTIVES: To examine whether simple cognitive tests, when applied to cognitively intact older persons, are useful predictors of cognitive impairment 7 years later. DESIGN: Cohort study. SETTING: Durham, North Carolina; East Boston, Massachusetts; and New Haven, Connecticut, areas that are part of the National Institute on Aging Established Populations for Epidemiological Studies of the Elderly. PARTICIPANTS: Participants, aged 70 to 79, from three community-based studies, who were in the top third of this age group, based on physical and cognitive functional status. MEASUREMENTS: New onset of cognitive impairment as defined by a score of less than 7 on the Short Portable Mental Status Questionnaire (SPMSQ) in 1995. RESULTS: At 7 years, 21.8% (149 of 684 subjects) scored lower than 7 on the SPMSQ. Using multivariate logistic regression, three baseline (1988) cognitive tests predicted impairment in 1995. These included two simple tests of delayed recall-the ability to remember up to six items from a short story and up to 18 words from recall of Boston Naming Test items. For each story item missed, the adjusted odds ratio (AOR) for cognitive impairment was 1.44 (95% confidence interval (CI) = 1.16-1.78, P <.001). For each missed item from the word list, the AOR was 1.20 (95% CI = 1.09-1.31, P <.001). The Delayed Recognition Span, which assesses nonverbal memory, also predicted cognitive impairment, albeit less strongly (odds ratio = 1.06 per each missed answer, 95% CI = 1.003-1.13, P =.04). CONCLUSIONS: This study identifies measures of delayed recall and recognition as significant early predictors of subsequent cognitive decline in high-functioning older persons. Future efforts to identify those at greatest risk of cognitive impairment may benefit by including these measures.

Aged↗
PubMed1998

[For active dermatocosmetics and free of unnecessary animal experimentation].

At the dawn of this century, dermocosmetology is at cross-roads because new European regulations are changing its face. The proof of claims must be given and the entire composition of the product must be released. In addition, animal testing is about to be banned. Such new regulations incite to search for and validate predictive tests aiming at the objective evaluation of the activity and tolerance claimed by dermocosmetic products. Such tests must be an alternative to unnecessary animal experimentation. These aspects are scrutinized scientifically by the EEMCO experts in combination with the ECVAM and COLIPA organizations.

Animal Testing Alternatives↗
PubMed1997

Prediction of postoperative venous thrombosis using haemostasis tests.

The prediction of patients who are at sufficiently high risk of postoperative deep venous thrombosis to indicate perioperative antithrombotic prophylaxis has traditionally used only clinical risk factors. The associations of preoperative and/or postoperative haemostatic tests with postoperative deep venous thrombosis are reviewed. In general, the results support the biological concept of a preoperative and postoperative prothrombotic tendency in patients who develop deep venous thrombosis. Increased levels of coagulation activation markers and decreased assays of fibrinolytic potential show consistent relationships to postoperative deep venous thrombosis. At present, however, the clinical utility of such tests is unproven; so that at present they cannot be advocated for routine preoperative or postoperative screening.

Biomarkers↗
PubMed1993

Efficacy of the sperm survival test for the prediction of oocyte fertilization in culture.

The present study was carried out to investigate the predictive value of the sperm survival test (SST) with respect to the fertilization of oocytes in culture. In general, our laboratory uses a total of 50,000-150,000 motile spermatozoa to inseminate each oocyte. The remaining material is evaluated for motility before and after 24 h of incubation at 37 degrees C in a 5% CO2 atmosphere. A total of 250 oocytes from 50 cases (mean +/- SD, 5.0 +/- 2.4 oocytes per retrieval) were inseminated and the final rate of cleaved embryos obtained was 52.5%. The SST (%) was considered normal when the ratio (final density of progressing spermatozoa after 24 h x 100/initial density of progressing spermatozoa) was 50% or more. Any other result was considered abnormal. Cases presenting one or more cleaved embryos (n = 40) were separated from those in which no embryo formation occurred (n = 10) and the results were compared in terms of the respective sperm survival rates over a period of 24 h: normal SST (one or more cleaved embryos, 37; none, five), abnormal SST (one or more cleaved embryos, three; none, five). The specificity of the SST was 0.92 and sensitivity 0.50, the predictive value of the abnormal test was 0.62 and the predictive value of the normal test 0.88. The efficacy of the test was estimated at 0.71, which was better than the conventional parameters of sperm analysis. A receiver-operating characteristics curve for SST confirmed that the test can be useful for the prediction of fertilizability of oocytes in the laboratory.

Adult↗
PubMed1990

Relationship of DNA ploidy to chemoresistance of tumors as measured by in vitro tests.

To examine whether patients with aneuploid tumors might derive more benefit from chemotherapy than would patients with diploid tumors, predictive tests for determining resistance in human tumors were carried out and the test results compared with the DNA ploidy of the corresponding tumors. Multidrug-resistance in 15 kidney carcinomas grown as primary cultures was determined by immunofluorescence by Mab C219, which is specific for the plasma membrane glyco-protein P-170, and by the use of tritiated nucleotide incorporation after addition of doxorubicin. Aneuploid tumors had a higher tendency to be more sensitive than diploid tumors, but the correlation was not significant. This was confirmed by reanalyzing our earlier data on ovarian and lung cancers. In conclusion, DNA measurement using flow cytometry does not appear to be a suitable tool for prediction of resistance of human tumors to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Technical feasibility of genetic testing for Alzheimer's disease.

This article examines the feasibility of using molecular genetic information for diagnostic and predictive testing in Alzheimer's disease (AD). The scope is limited largely to early onset familial cases, but a brief update on genetic research in late onset disease is included. The usefulness and accuracy of such testing is determined by the results and interpretation of current research data which are presented herein. The ethical and legal issues implicated in such procedures are not covered but are examined elsewhere in this issue. During the course of the genetic analysis of AD, it has become clear that it is an etiologically heterogeneous disorder. In understanding the genetic predisposition to AD there should be continual attention to this message. Age of onset and familiality have emerged as the most useful clinical features demarcating subgroups with common origins. At least two genes predispose (independently) to early onset familial AD: the beta-amyloid precursor protein gene (beta APP) and an unidentified gene on chromosome 14. Germ line mutations in these genes act dominantly. The accurate use of genetic data in AD, for diagnostic, screening and predictive purposes relies on the most up-to-date knowledge of the transmission of the disorder in relation to mutations in these genes. The interpretation of genetic data is examined for each of the known early onset genes. In addition, we review the data pertaining to late onset disease and risk conferred by the APOE locus to both familial and nonfamilial cases. The use of these data in genetic risk analysis must be reserved until a full explanation of the association and its meaning is forthcoming. Isolated cases of AD occur at all ages of onset, but no AD mutations in the beta APP gene have yet been identified in isolated cases.

Adult↗
PubMed1989

Hypoosmotic swelling test in the prediction of male fertility.

The hypoosmotic swelling test (HOS) is a simple test to measure the functional competence of human sperm membranes. The question is, does a relationship exist between this competence and the fertilization potential of human spermatozoa? In this study the strongest correlation (r = 0.76) was obtained between sperm swelling and sperm viability (supravital staining). Only a moderate correlation (r = 0.50) was obtained with normal sperm morphology; weaker correlations were also obtained with the sperm penetration assay (r = 0.42) and human IVF (r = 0.24). The results, therefore, indicate that the HOS test has a limited predictive value. Notwithstanding this low concordance between sperm swelling and fertilizing potential, a less than 50% HOS test threshold was seen to be a definite indicator of a male factor.

Cell Survival↗
PubMed2004

Low contrast vision function predicts subsequent acuity loss in an aged population: the SKI study.

Can vision tests predict subsequent loss of acuity? The association between performance on several low contrast spatial vision measures, glare recovery, color discrimination, flicker sensitivity, stereopsis and ocular disease status at baseline and acuity loss 4.4 years later was examined in a large aged random sample with good initial acuity. In univariate analyses, several vision measures, retinal disease status and age were each significant predictors of subsequent acuity loss. In a multiple regression analysis, only low contrast spatial vision was a significant predictor, but the other vision measures, retinal disease status and age were not. For each doubling of low contrast spatial vision threshold at baseline, individuals were more than two times as likely to suffer subsequent significant visual acuity loss. Tests of low contrast spatial vision are strong predictors of significant subsequent visual acuity loss. These findings have implications for clinical trials, clinical management, and acceptance of these measures into clinical practice.

Aged↗
PubMed1982

Alternatives to donor matching for control of graft-versus-host disease.

Graft-versus-host disease (GvHD) after bone-marrow transplantation in dogs is controlled by many different genetic systems. In littermate combinations identical for the major histocompatibility complex (MHC) the number of systems that influence GvHD is related to the number of donor lymphocytes injected. If the number of donor lymphocytes administered is sufficiently low, minor histocompatibility systems do not influence survival after bone-marrow transplantation. With increasing numbers of donor lymphocytes the beneficial influence of MHC matching on GvH incidence and severity disappears and minor histocompatibility antigens, coded for on at least two other autosomal chromosomes as well as possibly the Y chromosome, can cause severe GvHD. In contrast, the X chromosome does not appear to carry a histocompatibility system that is of relevance to GvHD control. The severity and tissue distribution of histological signs of GvHD in recipients of bone-marrow and lymph-node cells from MHC-identical donors are similar to those in recipients of MHC-mismatched bone-marrow cells. Female donors do appear to cause severe GvHD more frequently than males. In contrast to rhesus monkey and human bone-marrow cells, dog bone-marrow cells are negative in PHA tests. This is in accordance with the generally benign course of GvHD in dogs that are treated with bone-marrow cells only from histocompatible littermate donors. The influence of the sex of the bone-marrow donor on GvHD incidence and severity is not reflected in differences between PHA tests with male and female dog lymphocytes. A better predictive test for GvH potential than the PHA test appears to be needed. Alternatives to additional donor selection for the prevention of GvHD in histocompatible recipients appear to be the use of a male donor and the removal of lymphocytes from bone-marrow-cell suspensions prior to transplantation.

Animals↗
PubMed1984

Acute cystitis: a prospective study of laboratory tests and duration of therapy.

The efficacy of single-dose therapy with trimethoprim-sulfamethoxazole (TMP-SMZ) and the cost-effectiveness of routine urinalyses and cultures were studied in a prospective randomized trial of 200 women who presented with symptoms of acute lower urinary tract infection. Without the physician's knowledge of the results of urinalysis or culture, the patients were randomly assigned to receive either a single dose or a 10-day multiple-dose course of TMP-SMZ and were followed up for 6 months. Of the 136 patients with positive urine cultures, 68 received single-dose therapy with TMP-SMZ--10 of whom had relapses--and 68 received multiple-dose therapy with TMP-SMZ--only 2 of whom had relapses (P less than 0.02). Fifteen patients in each treatment group experienced reinfection. Side effects of rash and vaginitis were more common in patients who received multiple-dose therapy, but they were mild and well tolerated. Of the 51 patients with urethral syndrome, 48 became asymptomatic after therapy. None of the following tests predicted treatment outcome: pretreatment urinalysis, urine culture or susceptibility testing, antibody-coated bacteria testing, or routine follow-up urinalyses or urine cultures. Empiric therapy with TMP-SMZ in selected women with symptoms of acute uncomplicated urinary tract infection seems practical, safe, and cost-efficient. Considerable savings can be achieved by reserving urinalyses and urine cultures for patients with persistent or recurrent symptoms. Higher cure rates can be expected in patients who receive a standard 10-day course of therapy with TMP-SMZ compared with those who receive single-dose therapy with TMP-SMZ.

Acute Disease↗
PubMed2003

Cognitive-behavioural therapy with a Huntington's gene positive patient.

The treatment of choice for depression or anxiety after genetic testing is the use of medication. The present paper reports a case of a lady who had a positive test result for Huntington's disease (HD). After the predictive test her mood declined and she experienced symptoms of anxiety. Cognitive-behavioural therapy (CBT) enabled her to deal effectively with her negative automatic thoughts (NATs) and interpret situations more realistically. Therapy was successful in reducing her level of physical, behavioural and affective symptoms and in increasing her sense of control. These gains were maintained at 3 and 6 months in spite of the death of her mother. The paper discussed the potential value of cognitive-behavioural theory and therapy in similar cases.

Adult↗
PubMed2002

Predicting the risk of tick-borne diseases.

This brief review focuses on the value of predictive risk mapping and the question of how to test predictions of the spatial and temporal variation in risk of tick-borne diseases, specifically as caused by tick-borne encephalitis virus (TBEv). Predictions of the present distribution of TBEv, driven by satellite data, match the mapped records of TBE cases with 90% accuracy in the Baltic region and 81% accuracy in central Europe. Many of the apparently false predictions of TBE presence coincide with recent records of new or reactivated foci, and highlight regions for active surveillance. Predictions of the changes in TBEv distribution under the influence of climate change suggest that TBEv may be driven into increasingly high latitude and high altitude regions, until by the 2080s it is confined to parts of Scandinavia. This is consistent with the fact that enzootic TBEv cycles are inherently fragile and depend for their existence on specific seasonal temperature profiles and moisture conditions, which may be disrupted by climate change. Changes in the incidence of TBE in many countries since the 1990s are also consistent with these predictions, although there is evidence that local non-biological factors also play an important role in determining the incidence of disease.

Animals↗
PubMed2000

Environment-dependent residue contact energies for proteins.

We examine the interactions between amino acid residues in the context of their secondary structural environments (helix, strand, and coil) in proteins. Effective contact energies for an expanded 60-residue alphabet (20 aa x three secondary structural states) are estimated from the residue-residue contacts observed in known protein structures. Similar to the prototypical contact energies for 20 aa, the newly derived energy parameters reflect mainly the hydrophobic interactions; however, the relative strength of such interactions shows a strong dependence on the secondary structural environment, with nonlocal interactions in beta-sheet structures and alpha-helical structures dominating the energy table. Environment-dependent residue contact energies outperform existing residue pair potentials in both threading and three-dimensional contact prediction tests and should be generally applicable to protein structure prediction.

Algorithms↗
PubMed2006

Preclinical and clinical pharmacology of DOV 216,303, a "triple" reuptake inhibitor.

DOV 216,303 [(+/-)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane hydrochloride] is the prototype of a class of compounds referred to as "triple" reuptake inhibitors. Such compounds inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), the three neurotransmitters most closely linked to major depressive disorder. DOV 216,303 inhibits [(3)H]NE, [(3)H]5-HT, and [(3)H]DA uptake to the corresponding human recombinant transporters (expressed in HEK 293 cells) with IC(50) values of approximately 20, 14, and 78 nM, respectively. DOV 216,303 is active in tests predictive of antidepressant activity including the mouse forced swim test and reversal of tetrabenazine-induced ptosis and locomotor depression. The pharmacodynamic, pharmacokinetic, and toxicological profile of DOV 216,303 in animals prompted us to initiate clinical studies. In both single and multiple dose studies using normal volunteers, DOV 216,303 was safe and well-tolerated. Furthermore, both C(max) and AUC values were dose-proportional between 5-150 mg. The plasma concentrations of DOV 216,303 at doses >10 mg were in excess of the IC(50) values for inhibition of biogenic amine reuptake. In a Phase II study designed to explore the safety and tolerability of DOV 216,303 in depressed individuals, patients received either 100 mg DOV 216,303 (50 mg b.i.d.) or 40 mg citalopram (20 mg, b.i.d.) for two weeks. A placebo arm was not employed in this study because several institutional review boards required administration of an active control to severely depressed individuals. Time dependent reductions in HAM-D scores (the primary outcome measure) were observed in both the DOV 216,303 and citalopram groups compared to baseline scores (p < 0.0001). The side effect profile was not remarkably different between treatment arms. These findings provide preliminary evidence of a clinically meaningful antidepressant action with a molecule capable of inhibiting the three transmitters most closely linked to major depressive disorder.

Animals↗
PubMed2005

In vitro mutagenicity studies of the antiretrovirals AZT, Didanosine, and 3TC and a plant antiviral extract Secomet-V derived from the Trifollium species.

The plant extract Secomet-V has previously been shown by Kotwal et al. to have potent antiviral activity. It was tested for mutagenicity with the Ames gene mutation test in Salmonella and the chromosome damage (clastogenic) micronucleolus (MN) test in human lymphocytes. These tests predict long-term carcinogenesis activity of the agents tested. Secomet-V (with charcoal added) demonstrated weak clastogenic activity, but powerful mutagenic activity in the Ames test with the addition of exogenous metabolic activation. The mutagenic activity of the conventional antiretroviral drugs AZT, Didanosine (DID), and 3TC alone and in dual combinations was also assessed for the first time for Salmonella mutagenicity without any mutagenic effects. AZT, DID, and 3TC have also been tested for MN induction; DID and 3TC resulted negatively, whereas AZT was positive in a dose-related manner. The dual combinations of AZT and DID, 3TC and DID plus 3TC did not result in any additive or synergistic effect. Purification in the absence of charcoal results in a drastic reduction in extract mutagenicity, which is almost reduced completely by further ultrafiltration (cutoff <3,000 Da). This fraction, which is a mixture of molecules of less than 3,000 Da, still possesses the capability to induce sister chromatid exchanges in human lymphocytes. This could be due to residual mutagenicity or, more likely, to the slowdown of the DNA replication process. These findings open new possibilities for HIV therapy, because this antiviral activity of Secomet-V purified in the absence of charcoal and further filtered through a 3,000-Da filter is devoid of mutagenic activity and therefore safe for long-term use.

Anti-HIV Agents↗
PubMed1999

DNA analysis of Huntington's disease: five years of experience in Germany, Austria, and Switzerland.

OBJECTIVE: To review the direct DNA testing for Huntington's disease (HD) in Germany, Switzerland, and Austria from 1993 to 1997, and to analyze the population with regard to age structure, gender, and family history. METHODS: Twelve laboratories (nine in Germany, two in Austria, and one in Switzerland) recorded data pertaining to repeat number, gender, age at molecular diagnosis, and family history of probands. The molecular test was categorized as either diagnostic (for symptomatic individuals), presymptomatic (for individuals at risk), and prenatal (for pregnancies at risk). RESULTS: A total of 3,090 HD patients, 992 individuals at risk, and 24 fetuses were investigated using DNA analysis. The clinical diagnosis was confirmed in 65.6% of patients. A total of 38.5% of individuals at risk inherited an expanded CAG repeat. The female-to-male ratio showed a distinct predominance of women both in the diagnostic and presymptomatic groups. Of the fetuses tested, six were carriers of an expanded CAG repeat. Two pregnancies were interrupted; one pregnancy was not. No information about the parents' decision was obtained for the remaining three pregnancies. CONCLUSIONS: Approximately 20% of the estimated 10,000 HD patients living in Germany, Switzerland, and Austria have been identified by DNA analysis (total population, approximately 100 million; incidence of HD, 1:10,000). Assuming a ratio of HD patients to individuals at risk of 1:3, approximately 30,000 individuals are, in principle, eligible for a presymptomatic test. Less than 3 to 4% of individuals at risk have requested a presymptomatic test. This shows that the assumed enormous request of predictive testing has not occurred. More surprisingly, prenatal diagnoses were found to be rare.

Adult↗